Biochem - Metabolism (Sugar Metabolism & Disorders)

Question 1

Give 2 examples of disorders of fructose metabolism.

Answer 1

(1) Essential fructosuria (2) Fructose intolerance

Question 2

What is the defect in Essential fructosuria?

Answer 2

Involves a defect in fructokinase

Question 3

What is the mode of inheritance of essential fructosuria?

Answer 3

Autosomal recessive

Question 4

What kind of condition (in terms of severity) is essential fructosuria, and why?

Answer 4

A benign, asymptomatic condition, since fructose is not trapped in cells

Question 5

What are the symptoms of essential fructosuria?

Answer 5

Symptoms: Fructose appears in blood and urine

Question 6

How do fructose metabolism disorders compare/contrast to disorders of galactose metabolism in terms of severity of symptoms?

Answer 6

Disorders of fructose metabolism cause milder symptoms than analogous disorders of galactose metabolism.

Question 7

What causes fructose intolerance?

Answer 7

Hereditary deficiency of aldolase B.

Question 8

What is the mode of inheritance of fructose intolerance?

Answer 8

Autosomal recessive

Question 9

What is the pathogenesis of fructose intolerance?

Answer 9

Hereditary deficiency of aldolase B… Fructose 1-P accumulates, causing a decrease in available phosphate, which results in inhibition of glycogenolysis and gluconeogenesis.

Question 10

In what setting do fructose intolerance symptoms present?

Answer 10

Symptoms present following consumption of fruit, juice, or honey

Question 11

What will the urine dipstick results be in patients with fructose intolerance, and why? In general, what kind of sugar can be detected in the urine, and what is the clinical significance of this?

Answer 11

Urine dipstick will be negative (tests for glucose only); Reducing sugar can be detected in the urine (nonspecific test for inborn errors of carbohydrate metabolism)

Question 12

What are 4 symptoms associated with fructose intolerance?

Answer 12

Symptoms: hypoglycemia, jaundice, cirrhosis, vomiting

Question 13

What is the treatment for fructose intolerance?

Answer 13

Treatment: Decrease intake of both fructose and sucrose (glucose + fructose)

Question 14

Diagram the major steps of fructose metabolism in the liver, labeling the following key correlations: (1) Fructokinase deficiency = Essential fructosuria (2) Aldolase B deficiency = Fructose intolerance (3) Fructose bypasses rate-limiting step of glycolysis (PFK) via this pathway.

Answer 14

See p. 106 in First Aid 2014 for visual at bottom of page

Question 15

What are 2 disorders of galactose metabolism?

Answer 15

(1) Galactokinase deficiency (2) Classic galactosemia

Question 16

What is Galactokinase deficiency? What metabolic change occurs if galactose is present in the diet in a patient with this deficiency?

Answer 16

Hereditary deficiency of galactokinase. Galactitol accumulates if galactose is present in diet.

Question 17

What is the severity of galactokinase deficiency? What is its mode of inheritance?

Answer 17

Relatively mild condition. Autosomal recessive

Question 18

What are symptoms associated with galactokinase deficiency?

Answer 18

Symptoms: galactose appears in blood and urine, infantile cataracts. May initially present as failure to track objects or to develop a social smile.

Question 19

What causes classic galactosemia?

Answer 19

Absence of galactose-1-phosphate uridyltransferase.

Question 20

What is the mode of inheritance of classic galactosemia?

Answer 20

Autosomal recessive

Question 21

What causes damage in classic galactosemia?

Answer 21

Damage is caused by accumulation of toxic substances (including galactitol, which accumulates in the lens of the eye).

Question 22

What are 5 symptoms associated with classic galactosemia?

Answer 22

Symptoms: failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability

Question 23

What is the treatment for classic galactosemia?

Answer 23

Treatment: exclude galactose and lactose (galactose + glucose) from diet

Question 24

For enzymes associated with severe deficiencies: Fructose is to ____ as Galactose is to ____ .

Answer 24

Fructose is the Aldolase B as Galactose is to UridylTransferase; Think: “FAB GUT”

Question 25

What metabolic change results from the more serious defects of galactose metabolism?

Answer 25

The more serious defects lead to (PO4)3- depletion

Question 26

What condition can classic galactosemia cause in neonates?

Answer 26

Classic galactosemia can lead to E. coli sepsis in neonates

Question 27

Diagram the major steps in galactose metabolism, including the activity of the following enzymes: (1) Aldose reductase (2) Galactokinase (3) Uridyltransferase. Also, label the link to glycolysis/gluconeogenesis.

Answer 27

See p. 107 in First Aid 2014 for visual near top left of page

Question 28

What is the purpose of converting glucose to sorbitol? What enzyme does this?

Answer 28

An alternative method of trapping glucose in the cell (besides converting it to G-6-P through Hexokinase/Glucokinase) is to convert it to its alcohol counterpart, called sorbitol, via aldolase reductase

Question 29

What is the role of sorbitol dehydrogenase?

Answer 29

(After aldolase reductease converts glucose to sorbitol) Some tissues then convert sorbitol to fructose using sorbitol dehydrogenase

Question 30

What kind of damage can result from an insufficient amount of sorbitol dehydrogenase, and why? Give 3 examples of conditions that may result.

Answer 30

Tissues with an insufficient amount of this enzyme are at risk for intracellular sorbitol accumulation, causing osmotic damage (e.g., cataracts, retinopathy, and peripheral neuropathy seen with chronic hyperglycemia in patients)

Question 31

What happens to galactose when it is at high bood levels? What enzyme catalyzes this?

Answer 31

High blood levels of galactose also result in conversion to the osmotically active galactitol via aldose reductase

Question 32

Which 3 organs/body parts have both aldose reductase and sorbitol dehydrogenase enzymes?

Answer 32

(1) Liver, (2) Ovaries, and (3) Seminal vesicles have both enzymes.

Question 33

What 3 organs/body parts have only aldose reductase? What is an additional organ/body part noted for having primarily adolase reductase?

Answer 33

(1) Schwann cells, (2) Retina, and (3) Kidneys have only aldose reductase; Lens has primarily aldose reductase.

Question 34

Draw the reactions catalyzed by Aldose reductase and Sorbitol dehydrogenase in organs/body parts that have both enzymes.

Answer 34

See p. 107 in First Aid 2014 for visual near bottom-middle of page

Question 35

Draw the reaction catalyzed by Aldose reductase in organs/body parts that have only or primarily this enzyme.

Answer 35

See p. 107 in First Aid 2014 for visual near bottom-middle of page

Question 36

What is lactase deficiency? What is the normal function of lactase, and where does it function ?

Answer 36

Insufficient lactase enzyme => dietary lactose intolerance. Lactase functions on the brush border to digest lactose (in human and cow milk) into glucose and galactose

Question 37

What defines primary lactase deficiency? In what patient populations is it common?

Answer 37

Primary: age-dependent decline after childhood (absence of lactase-persistent allele), common in people of Asian, African, or Native American descent

Question 38

What defines secondary lactase deficiency?

Answer 38

Secondary: loss of brush border due to gastroenteritis (e.g., rotavirus), autoimmune disease, etc.

Question 39

What defines congenital lactase deficiency?

Answer 39

Congenital lactase deficiency: rare, due to defective gene

Question 40

What stool and breath findings occur with lactose intolerance test in a lactase deficient patient?

Answer 40

Stool demonstrates low pH and breath shows high hydrogen count with lactose intolerance test

Question 41

What describes the intestinal biopsy in patients with hereditary lactose intolerance?

Answer 41

Intestinal biopsy reveals normal mucosa in patients with hereditary lactose intolerance

Question 42

What are 4 symptoms/findings associated with lactase deficiency?

Answer 42

Bloating, cramps, flatulence, osmotic diarrhea

Question 43

What is the treatment for lactase deficiency?

Answer 43

Avoid dairy products or add lactase pills to diet; Lactose-free milk